BIONANOSMART_DDS · Biopolymer-Based Nanoparticle “Smart” Drug Delivery Systems and their Biopharmaceutical Application by Oral Administration

Biopolymer-Based Nanoparticle “Smart” Drug Delivery Systems and their Biopharmaceutical Application by Oral Administration

Bioinspired nanoparticles engendered from bioresponsive natural polymers could serve as vehicles to deliver drugs in much more efficient ways. This project aimed to design a new type of hybrid nanoparticles obtained by ionotropic gelation and covalent cross-linked of their surface based on chitosan and other polysaccharides (e.g. alginate), to characterize in detail their biophysical properties and investigate their potential application as advanced drug delivery nanocarriers intended for oral administering of metronidazol and insulin, as a route to achieve potential innovative therapies in the localized treatment of stomach infection by Helicobacter pylori and diabetes Type I, respectively. In parallel, they set the foundations to the development a second platform of "smart" nanoparticles with the capacity to interfere with communication processes among Gram (-) bacteria, known as quorum sensing, as a route to identify novel strategies to inhibit their pathogenic response in humans and plants. The developed particles were studied by a range of techniques that were new to Dr Goycoolea, such as dynamic light scattering (DLS), transmission electron microscopy (TEM) and synchrotron small-angle X ray scattering (SAXS). A core-shell structure was identified by TEM and confirmed by SAXS studies carried at the European Synchrotron Research Facility (ESRF) in Grenoble. The thickness of this shell is somewhat lower at pH 4.5 than in simulated gastric fluid (SGF, pH 1.2). The in vitro release of metronidazol was found to be twice as much at pH 4.5 than at 1.2. This behavior is what is sought for treatments against Helicobacter pylori localized in the stomach. The capacity of pH-sensitive nanoparticles to associate and release insulin in vitro and after oral delivery to healthy rats was also investigated. All systems showed a high insulin association efficiency (> 80%). Interesting, genipin crosslinking resulted in a full association of the peptide to the NPs. The in vitro release properties of insulin was investigated in SGF and simulated intestinal fluid (pH 6.8). It was found that the developed particles did prevent the premature release of the peptide in SGF, while in SIF they were able to release a portion of the payload; meanwhile conventional nanoparticles released most of the peptide in SGF. Preliminary assays of oral administering to healthy rat (30 IU/kg) were initiated and are not yet conclusive. The second class of "smart" nanoparticles were intended for selectively recognize and adsorb bacterial metabolites involved in "quorum sensing" (QS) of Gram (-) bacteria, as an strategy to exert a selective targeting and interfere with the pathogenic and virulent responses. To this end, a chemical strategy was designed so as to modify the surface of the nanoparticles to confer it affinity to bacterial metabolites well-known to mediate QS processes in a large number of bacterial species. The effect of these NPs has been tested against a modified E. coli used as a biosensor of QS. So far, the results look very promissing and the MIP-NPs seem to exhibit capacity to inhibit the expression of the genes involved in QS controlled by AHL. The potential outreach of the results of this project is evident as innovative solutions in the therapy against H. pylori infection using pH-sensitive nanoparticles for stomach-localized effect could be highly beneficial to pharmaceutical companies and to human health. Similarly, the impact of potential new strategies towards the search of an effective nanoparticle oral delivery platform for administering of insulin, bears enormous benefit in diabetes therapy. Besides, to quench bacterial metabolites can also be envisaged to bear an enormous potential as a new strategy that could result in the reduction of the amounts of antibiotics used and in the prevention of bacterial resistance. This is relevant not only to the human health sector, but also to veterinary, agriculture, aquaculture, among other.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз